Substituted oxazoles and thiazoles derivatives as hPPARγ and hPPARα activators

Abstract

The present invention discloses compounds of formula (I), and tautomeric forms, pharmaceutically acceptable salts, or solvates thereof. Preferably, the compounds of the invention are dual activators of hPPARgamma and hPPAR{acute over (alpha.

What is claimed is:  
     
       1. A compound of formula (I), or a tautomeric form, pharmaceutically acceptable salt, or solvate thereof,                    
       wherein; 
       R 1  is hydrogen or C 1-3 alkyl;  
       R 2  is hydrogen, or C 1-8 alkyl optionally substituted by one or more halogens;  
       R 3  is C 1-6 alkyl, C 4-7 cycloalkyl or cycloalkenyl, —OC 1-6 alkyl, —NR′R′ (where each R′ is independently hydrogen or C 1-3 alkyl), a 5 or 6 membered heterocyclic group containing at least one oxygen, nitrogen, or sulfur ring atom (optionally substituted by one or more halogen, C 1-6 alkyl optionally substituted by one or more halogens, —OC 1-6 alkyl optionally substituted by one or more halogens, —CN, or —NO 2 ), or phenyl (optionally substituted by one or more halogen, C 1-6 alkyl optionally substituted by one or more halogens, —OC 1-6 alkyl optionally substituted by one or more halogens, —CN, or —NO 2 );  
       R 4  is a 5 or 6 membered heterocyclic group containing at least one oxygen, nitrogen, or sulfur ring atom (optionally substituted by one or more halogen, C 1-6 alkyl optionally substituted by one or more halogens, —OC 1-6 alkyl optionally substituted by one or more halogens, —CN, or —NO 2 ), or phenyl (optionally substituted by one or more halogen, C 1-6 alkyl optionally substituted by one or more halogens, —OC 1-6 alkyl optionally substituted by one or more halogens, —NR′R′, —CN, or —NO 2 );  
       R 5  is hydrogen, halogen, or C 1-3 alkyl optionally substituted by one or more halogens;  
       R 6  is hydrogen or C 1-3 alkyl;  
       X is O or S; and  
       n is 1, 2, or 3.  
     
     
       2. A compound of  claim 1  wherein R 1  is hydrogen or methyl. 
     
     
       3. A compound of  claim 1  wherein R 2  is C 1-8 alkyl optionally substituted by one or more halogens. 
     
     
       4. A compound of  claim 1  wherein R 3  is, pyridine, pyrazine, thiophene, furan, thiazole, or phenyl (any of which may be optionally substituted by one or more halogen, C 1-6 alkyl optionally substituted by one or more halogens, —OC 1-6 alkyl optionally substituted by one or more halogens, —CN, or —NO 2 ) or C 4-7 cycloalkyl. 
     
     
       5. A compound of  claim 4  wherein R 3  is phenyl (optionally substituted by one or more halogen, C 1-6 alkyl optionally substituted by one or more halogens, —OC 1-6 alkyl optionally substituted by one or more halogens, —CN, or —NO 2 ). 
     
     
       6. A compound of  claim 1  wherein R 4  is phenyl (optionally substituted by one or more halogen, C 1-6 alkyl optionally substituted by one or more halogens, or —OC 1-6 alkyl optionally substituted by one or more halogens). 
     
     
       7. A compound of  claim 1  wherein R 5  is hydrogen, or C 1-3 alkyl optionally substituted by one or more halogens. 
     
     
       8. A pharmaceutical composition according to  claim 7  further comprising a pharmaceutically acceptable diluent or carrier. 
     
     
       9. A compound of  claim 1  wherein R 6  is methyl or ethyl. 
     
     
       10. A compound of  claim 1  selected from the group consisting of: 
       (2S)- 2- {[(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-3-(4-{2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-(4-{2-[2-(4-isopropoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-(4-{2-[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-2-{[(Z)-1-ethyl-3-oxo-3-phenyl-1-propenyl]amino}-3-[4-(2-{5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}ethoxy)phenyl]propanoic acid;  
       (2S)-2-{[(Z)-1-ethyl-3-(4-fluorophenyl)-3-oxo-1-propenyl]amino}-3-(4-{2-[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}-3-[4-(2-{5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}ethoxy)phenyl]propanoic acid;  
       (2S)-2-{[(Z)-1-ethyl-3-oxo-3-phenyl-1-propenyl]amino}-3-(4-{2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-2-{[(Z)-1-ethyl-3-(4-fluorophenyl)-3-oxo-1-propenyl]amino}-3-(4-{2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-{4-[2-(5-methyl-2-phenyl-1,3-thiazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-3-(4-fluorophenyl)-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-(2,3,4-trifluorophenyl)-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-(4-nitrophenyl)-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-ethyl-3-(4-fluorophenyl)-3-oxo-1-propenyl]amino}-3-(4-{2-[2-(4-isopropoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-(2,4,5-trifluorophenyl)-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-ethyl-3-oxo-3-phenyl-1-propenyl]amino}-3-(4-{2-[2-(4-isopropoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-(4-methylphenyl)-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-ethyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-3-(4-{2-[2-(4-fluorophenyl)-5-methyl-1,3-thiazol-4-yl]ethoxy}phenyl)-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-(4-{2-[2-(4-fluorophenyl)-5-methyl-1,3-thiazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-2-{[(Z)-1-butyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-3-(4-chlorophenyl)-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-(3-nitrophenyl)-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-({(Z)-3-[2-fluoro-3-(trifluoromethyl)phenyl]-1-methyl-3-oxo-1-propenyl}amino)-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-3-(4-isopropoxyphenyl)-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-3-(2-chlorophenyl)-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-3-(2-furyl)-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-(2-pyrazinyl)-1-propenyl]amino}-3-{4-[2-(5-methyl-2phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-3-(2,4-difluorophenyl)-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-(1,3-thiazol-2-yl)-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-(3-thienyl)-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3oxo-3-(2-pyridinyl)-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-ethyl-3-(4-fluorophenyl)-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino3-{4-[2-(5-methyl-2-phenyl-1,3-thiazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-3-(2-fluorophenyl)-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-3-(2,3-difluorophenyl)-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-3-(2-hydroxyphenyl)-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}-2-{[(Z)-3oxo-3-phenyl-1-propyl-1-propenyl]amino}propanoic acid;  
       (2S)-2-{[(Z)-3-(4-methoxyphenyl)-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-3-(4-{2-[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)-2-{[(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}propanoic acid;  
       (2S)-2-{[(Z)-3-cyclohexyl-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-3-(4-{2-[2-(4-isopropoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)-2-{[(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}propanoic acid;  
       (2S)-2-{[(Z)-1-heptyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-(3-methylphenyl)-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-ethyl-3-oxo-3-phenyl-1-propenyl]amino}-3-(4-{2-[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]phenyl)propanoic acid;  
       (2S)-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-{4-[2-(5-methyl-2-phenyl-1,3-thiazol-4-yl)ethoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-(4-{2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-(4-{2-[2-(4-isopropoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-(4-{2-[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-3-(4-{2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-2-{([(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl}propanoic acid;  
       (2S)-3-{4-[2-(5-ethyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}-2-{([(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[2-(2-phenyl-5-propyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propoxy]phenyl}propanoic acid;  
       (2S)-3-{4-[2-(5-ethyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-{4-[3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-{4-[2-(5-ethyl-2-phenyl-1,3-thiazol-4-yl)ethoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-(4-{2-[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]ethoxy}phenyl)-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-(4-{3-[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]propoxy}phenyl)-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-(4-{2-[5-ethyl-2-(4-fluorophenyl)-1,3-thiazol-4-yl]ethoxy}phenyl)-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-(4-{3-[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]propoxy}phenyl)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-{4[3-(5-ethyl-2-phenyl-1,3-oxazol-4-yl)propoxy]phenyl}propanoic acid;  
       (2S)-3-(4-{3-[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]propoxy}phenyl)-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-{4-[3-(5-ethyl-2-phenyl-1,3-oxazol-4-yl)propoxy]phenyl}-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-{4-[3-(5-ethyl-2-phenyl-1,3-oxazol-4-yl)propoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-{4-[(5-ethyl-2-phenyl-1,3-thiazol-4-yl)methoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-{4-[(5-ethyl-2-phenyl-1,3-thiazol-4-yl)methoxy]phenyl}-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-{4-[(5-ethyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-(4-{[(5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]methoxy{phenyl)-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-{4-[(5ethyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl}propanoic acid;  
       (2S)-3-(4-{[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]methoxy}phenyl)2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-{4-[(5-ethyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl}-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-(4-{[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]methoxy}phenyl)-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-{4-[(5-ethyl-2-phenyl-1,3-thiazol-4-yl)methoxy]phenyl}propanoic acid;  
       (2S)-3-(4-{2-[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]ethoxy}phenyl)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-(4-{2-[5-ethyl-2-(4-fluorophenyl)-1,3-thiazol-4-yl]ethoxy}phenyl)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-{4-[2-(5-ethyl-2-phenyl-1,3-thiazol-4-yl)ethoxy]phenyl}propanoic acid;  
       and pharmaceutically acceptable salts and solvates thereof. 
     
     
       11. A compound of  claim 1  selected from the group consisting of 
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-ethyl-3-oxo-3-phenyl-1-propenyl]amino}-3-[4-(2-{5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}ethoxy)phenyl]propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-(2,3,4-trifluorophenyl)-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-(4-nitrophenyl)-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-(2,4,5-trifluorophenyl)-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-1-ethyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-3-(4-{2-[2-(4-fluorophenyl)-5-methyl-1,3-thiazol-4-yl]ethoxy}phenyl)-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-(4-{2-[2-(4-fluorophenyl)-5-methyl-1,3-thiazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-2-{[(Z)-1-butyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-2-{[(Z)-3-(4-chlorophenyl)-1-methyl-3-oxo-1-propenyl]amino}-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}propanoic acid;  
       (2S)-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-propyl-1-propenyl]amino}propanoic acid;  
       (2S)-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-(4-{2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-(4-{2-[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)propanoic acid;  
       (2S)-3-(4-{2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}phenyl)-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl}propanoic acid;  
       (2S)-3-{4-[2-(5-ethyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}-2-{[(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}propanoic acid;  
       (2S)-2-{[(Z)-1-methyl-3-oxo-3-phenyl-1-propenyl]amino}-3-{4-[3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propoxy]phenyl}propanoic acid;  
       (2S)-3-{4-[2-(5-ethyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-{4-[2-(5-ethyl-2-phenyl-1,3-thiazol-4-yl)ethoxy]phenyl}-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-(4-{2-[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]ethoxy}phenyl)-2-{[(Z)-3-oxo-3phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-(4-{3-[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]propoxy}phenyl)-2{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-(4-{2-[5-ethyl-2-(4-fluorophenyl)-1,3-thiazol-4-yl]ethoxy}phenyl)-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-(4-{3-[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]propoxy}phenyl)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-2-({(Z)-1-ethyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)-3-{4-[3-(5-ethyl-2-phenyl-1,3-oxazol-4-yl)propoxy]phenyl}propanoic acid;  
       (2S)-3-(4-{3-[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]propoxy}phenyl)-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-{4-[3-(5-ethyl-2-phenyl-1,3-oxazol-4-yl)propoxy]phenyl}-2-({(Z)-1-methyl-3-oxy-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-(4-{[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]methoxy}phenyl)-2-{[(Z)-3-oxo-3-phenyl-1-(trifluoromethyl)-1-propenyl]amino}propanoic acid;  
       (2S)-3-{4-[(5-ethyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl}-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-(4-{[5-ethyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]methoxy}phenyl)-2-({(Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl}amino)propanoic acid;  
       (2S)-3-(4-{2-[5-ethyl-2-(4-fluorophenyl)-1,3-thiazol-4-yl]ethoxy}phenyl)-2-({(Z)-1-ethyl-3-oxo-3-[4-trifluoromethyl)phenyl]-1propenyl}amino)propanoic acid;  
       and pharmaceutically acceptable salts and soivates thereof. 
     
     
       12. A compound of  claim 1  wherein said compound is a dual activator of hPPARγ and hPPARα. 
     
     
       13. A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 1 . 
     
     
       14. A pharmaceutical composition of  claim 13  further comprising a pharmaceutically acceptable diluent or carrier.